The etiology and pathogenesis of rheumatic and arthritic diseases remain obscure. Meanwhile, the need continues for safer, better tolerated drugs which will slow the progress and alleviate the symptoms of inflammatory diseases. For example, in rheumatoid arthritis any agent which reduces the inflammation is important in lessening or delaying the development of crippling.
The 3,3-dialkyl-1-(substituted-phenyl)triazene-1-oxides of the present invention represent a novel class of nonsteroidal compounds useful in the treatment of the inflammatory process.
Compounds related to those of the present invention include a class of 3-(substituted-phenyl)-1-alkyltriazene-1-oxides described as insecticides in Belgian Pat. No. 744930. Compounds of said patent are actually described as 1-(substituted-phenyl)-3-alkyl-3-hydroxytriazenes, but similar compounds are proven in Tetrahedron Letters No. 30, pp. 2593-2596 (1965) to be predominantly the 3-(substituted-phenyl)-1-alkyltriazene-1-oxide isomers. The order of numbering of the position of substituents on triazene-oxides and hydroxytriazenes is reversed.
Triazene-1-oxides are readily prepared by those skilled in the art. The method of preparation listed in Beilstein XVI, 742 and similar to that employed in the present invention, consists of reacting an unsymmetrical hydrazine, namely .alpha.-methyl-.alpha.-phenylhydrazine or .alpha.-diphenylhydrazine, with a substituted nitrosobenzene.
The 1-(substituted-phenyl)-3-hydroxy-3-methyltriazenes, isomeric to 3-(substituted-phenyl)-1-methyltriazene-1-oxides, are also described in Belgian Pat. No. 791,322 as immunosupressive agents. The method of preparation described therein consists of reacting an aniline with nitrous acid followed by a hydroxylamine. All of the above mentioned compounds differ from the compounds of the present invention in the position of attachment on the triazene of the substituted phenyl and alkyl groups.